Reviewed, UniProtKB/Swiss-Prot P04233 (HG2A_HUMAN)

Names and origin

Protein names

Recommended name:
    HLA class II histocompatibility antigen gamma chain
Alternative name(s):
    HLA-DR antigens-associated invariant chain
    Ia antigen-associated invariant chain
      Short name=Ii
    p33
    CD_antigen=CD74

Gene names

Name:	CD74
Synonyms:	DHLAG

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	296 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place. Serves as cell surface receptor for the cytokine MIF.
Subunit structure	Nonamer composed of three alpha/beta/gamma heterotrimers.
Subcellular location	Membrane; Single-pass type II membrane protein Potential.
Sequence similarities	Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Biological process	Immune response
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein Phosphoprotein Proteoglycan
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	T cell selection Non-traceable author statement. Source: UniProtKB antigen processing and presentation of endogenous antigen Non-traceable author statement. Source: UniProtKB cell proliferation Ref.12 Inferred from direct assay. Source: UniProtKB immunoglobulin mediated immune response Inferred from sequence or structural similarity. Source: UniProtKB intracellular protein transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptosis Ref.12 Inferred from direct assay. Source: UniProtKB prostaglandin biosynthetic process Ref.12 Inferred from direct assay. Source: UniProtKB protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of macrophage activation Ref.12 Non-traceable author statement. Source: UniProtKB signal transduction Ref.12 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to membrane Ref.1 Traceable author statement. Source: ProtInc intracellular Ref.12 Traceable author statement. Source: UniProtKB
Molecular function	MHC class II protein binding Non-traceable author statement. Source: UniProtKB cytokine binding Ref.12 Inferred from physical interaction. Source: UniProtKB identical protein binding Ref.12 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P04233-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P04233-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     209-272: Missing.

Isoform 3 (identifier: P04233-3)

The sequence of this isoform differs from the canonical sequence as follows:
     148-160: NADPLKVYPPLKG → SHWNWRTRLLGWV
     161-296: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 296

296

HLA class II histocompatibility antigen gamma chain

PRO_0000067954

Regions

Topological domain

1 – 46

46

Cytoplasmic Potential

Transmembrane

47 – 72

26

Signal-anchor for type II membrane protein Potential

Topological domain

73 – 296

224

Extracellular Potential

Domain

210 – 271

62

Thyroglobulin type-1

Region

103 – 117

15

CLIP

Amino acid modifications

Modified residue

25

1

Phosphoserine By similarity

Glycosylation

130

1

N-linked (GlcNAc...)

Glycosylation

136

1

N-linked (GlcNAc...) Ref.13

Glycosylation

282

1

O-linked (Xyl...) (glycosaminoglycan) Potential

Disulfide bond

213 ↔ 232

By similarity

Disulfide bond

243 ↔ 250

By similarity

Disulfide bond

252 ↔ 271

By similarity

Natural variations

Alternative sequence

148 – 160

13

NADPL…PPLKG → SHWNWRTRLLGWV in isoform 3.

VSP_037869

Alternative sequence

161 – 296

136

Missing in isoform 3.

VSP_037870

Alternative sequence

209 – 272

64

Missing in isoform 2.

VSP_005331

Experimental info

Sequence conflict

167

1

R → T in CAA27047. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

296

Helix Strand Turn

Details...

Helix

139 – 149

11

Helix

162 – 172

11

Helix

175 – 194

20

Helix

212 – 217

6

Beta strand

240 – 244

5

Turn

245 – 248

4

Beta strand

249 – 253

5

Beta strand

265 – 267

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified April 16, 2002. Version 3. Checksum: 27A13F252D5FB91D	FASTA	296	33,516
	10 20 30 40 50 60 MHRRRSRSCR EDQKPVMDDQ RDLISNNEQL PMLGRRPGAP ESKCSRGALY TGFSILVTLL 70 80 90 100 110 120 LAGQATTAYF LYQQQGRLDK LTVTSQNLQL ENLRMKLPKP PKPVSKMRMA TPLLMQALPM 130 140 150 160 170 180 GALPQGPMQN ATKYGNMTED HVMHLLQNAD PLKVYPPLKG SFPENLRHLK NTMETIDWKV 190 200 210 220 230 240 FESWMHHWLL FEMSRHSLEQ KPTDAPPKVL TKCQEEVSHI PAVHPGSFRP KCDENGNYLP 250 260 270 280 290 LQCYGSIGYC WCVFPNGTEV PNTRSRGHHN CSESLELEDP SSGLGVTKQD LGPVPM
	Isoform 2 (Short). Checksum: 5144439D0FD27C99	FASTA	232	26,399
	10 20 30 40 50 60 MHRRRSRSCR EDQKPVMDDQ RDLISNNEQL PMLGRRPGAP ESKCSRGALY TGFSILVTLL 70 80 90 100 110 120 LAGQATTAYF LYQQQGRLDK LTVTSQNLQL ENLRMKLPKP PKPVSKMRMA TPLLMQALPM 130 140 150 160 170 180 GALPQGPMQN ATKYGNMTED HVMHLLQNAD PLKVYPPLKG SFPENLRHLK NTMETIDWKV 190 200 210 220 230 FESWMHHWLL FEMSRHSLEQ KPTDAPPKES LELEDPSSGL GVTKQDLGPV PM
	Isoform 3. Checksum: 95CB3D7226497DE8	FASTA	160	18,328
	10 20 30 40 50 60 MHRRRSRSCR EDQKPVMDDQ RDLISNNEQL PMLGRRPGAP ESKCSRGALY TGFSILVTLL 70 80 90 100 110 120 LAGQATTAYF LYQQQGRLDK LTVTSQNLQL ENLRMKLPKP PKPVSKMRMA TPLLMQALPM 130 140 150 160 GALPQGPMQN ATKYGNMTED HVMHLLQSHW NWRTRLLGWV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure." Claesson L., Larhammar D., Rask L., Peterson P.A. Proc. Natl. Acad. Sci. U.S.A. 80:7395-7399(1983) [PubMed: 6324166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity." Strubin M., Mach B., Long E.O. EMBO J. 3:869-872(1984) [PubMed: 6586420] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens." Kudo J., Chao L.-Y., Narni F., Saunders G.F. Nucleic Acids Res. 13:8827-8841(1985) [PubMed: 3001652] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2).
[4]	"Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes." O'Sullivan D.M., Larhammar D., Wilson M.C., Peterson P.A., Quaranta V. Proc. Natl. Acad. Sci. U.S.A. 83:4484-4488(1986) [PubMed: 3459184] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). Tissue: Liver.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Heart and Synovium.
[7]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: B-cell and Tonsil.
[10]	Bienvenut W.V. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 22-35; 81-94; 171-179 AND 273-288, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[11]	"HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides." Riberdy J.M., Newcomb J.R., Surman M.J., Barbosa J.A., Cresswell P. Nature 360:474-477(1992) [PubMed: 1448172] [Abstract] Cited for: PROTEIN SEQUENCE OF 97-120.
[12]	"MIF signal transduction initiated by binding to CD74." Leng L., Metz C.N., Fang Y., Xu J., Donnelly S., Baugh J., Delohery T., Chen Y., Mitchell R.A., Bucala R. J. Exp. Med. 197:1467-1476(2003) [PubMed: 12782713] [Abstract] Cited for: INTERACTION WITH MIF.
[13]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136, MASS SPECTROMETRY. Tissue: Liver.
[14]	"The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3." Ghosh P., Amaya M., Mellins E., Wiley D.C. Nature 378:457-462(1995) [PubMed: 7477400] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 103-117.
[15]	"Structure of a trimeric domain of the MHC class II-associated chaperonin and targeting protein Ii." Jasanoff A., Wagner G., Wiley D.C. EMBO J. 17:6812-6818(1998) [PubMed: 9843486] [Abstract] Cited for: STRUCTURE BY NMR OF 134-208.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

K01144 mRNA. Translation: AAA36304.1. Different initiation.
X00497 mRNA. Translation: CAA25192.1.
X00497 mRNA. Translation: CAA25193.1.
X03339 Genomic DNA. Translation: CAA27046.1.
X03340 Genomic DNA. Translation: CAA27047.1.
M13560 , M13555, M13556, M13558, M13559 Genomic DNA. Translation: AAA36033.1.
BT019505 mRNA. Translation: AAV38312.1.
AK292076 mRNA. Translation: BAF84765.1.
AK297889 mRNA. Translation: BAG60210.1.
AC011372 Genomic DNA. No translation available.
AC011388 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61727.1.
CH471062 Genomic DNA. Translation: EAW61728.1.
CH471062 Genomic DNA. Translation: EAW61731.1.
BC018726 mRNA. Translation: AAH18726.1.
BC024272 mRNA. Translation: AAH24272.1.

IPI

IPI00022933.
IPI00217775.
IPI00607573.

PIR

HLHUG. A93981.

RefSeq

NP_001020329.1.
NP_001020330.1.
NP_004346.1.

UniGene

Hs.436568

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A6A	X-ray	2.75	C	103-117	[»]
1ICF	X-ray	2.00	I/J	210-274	[»]
1IIE	NMR	-	A/B/C	134-208	[»]
1L3H	NMR	-	A	210-274	[»]
1MUJ	X-ray	2.15	C	97-122	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P04233.

PTM databases

PhosphoSite

P04233.

Proteomic databases

PRIDE

P04233.

Genome annotation databases

Ensembl

ENST00000009530; ENSP00000009530; ENSG00000019582; Homo sapiens. [Genome view]
ENST00000353334; ENSP00000230685; ENSG00000019582; Homo sapiens. [Genome view]
ENST00000377795; ENSP00000367026; ENSG00000019582; Homo sapiens. [Genome view]

GeneID

972.

UCSC

uc003lsc.1. human.
uc003lsd.1. human.

Organism-specific databases

CTD

972.

GeneCards

GC05M149753.

H-InvDB

HIX0005314.

HGNC

HGNC:1697. CD74.

HPA

CAB002506.
HPA010592.

MIM

142790. gene.

PharmGKB

PA26236.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04233.

HOVERGEN

P04233.

Gene expression databases

ArrayExpress

P04233.

Bgee

P04233.

CleanEx

HS_CD74.

Genevestigator

P04233.

GermOnline

ENSG00000019582. Homo sapiens.

Family and domain databases

InterPro

IPR016333. HLA_II_histocompat_Ag_gsu.
IPR015386. MHC_II-assoc_invar/CLIP_MHC-bd.
IPR011988. MHC_II-assoc_invariant_trimer.
IPR000716. Thyroglobulin_1.
[Graphical view]

Gene3D

G3DSA:1.10.870.10. MHCII_invariant. 1 hit.
G3DSA:4.10.800.10. Thyroglobulin_1. 1 hit.

Pfam

PF09307. MHC2-interact. 1 hit.
PF08831. MHCassoc_trimer. 1 hit.
PF00086. Thyroglobulin_1. 1 hit.
[Graphical view]

PIRSF

PIRSF001992. CD74_antigen. 1 hit.

SMART

SM00211. TY. 1 hit.
[Graphical view]

PROSITE

PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4068.

PMAP-CutDB

P04233.

SOURCE

Search...

Entry information

Entry name

HG2A_HUMAN

Accession

Primary (citable) accession number: P04233
Secondary accession number(s): A8K7R1 , B4DNE8, Q14597, Q29832, Q5U0J8, Q8SNA0, Q8WLP6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	April 16, 2002
Last modified:	October 13, 2009
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.