Q8IZU9 (KIRR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kin of IRRE-like protein 3

Alternative name(s):
Kin of irregular chiasm-like protein 3
Nephrin-like protein 2

Gene names

Name:	KIRREL3
Synonyms:	KIAA1867, NEPH2
ORF Names:	UNQ5923/PRO4502/PRO19814

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	778 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Could be involved in the hematopoietic supportive capacity of stroma cells By similarity.
Subunit structure	Interacts with the C-terminus of NPHS2/podocin. Interacts with CASK. Ref.1 Ref.6
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.6.
Tissue specificity	Expressed in fetal and adult brain. Also expressed in kidney, specifically in podocytes of kidney glomeruli. Ref.1 Ref.6
Involvement in disease	A chromosomal aberration involving KIRREL3 and CDH15 is found in a patient with severe mental retardation and dysmorphic facial features. Translocation t(11;16)(q24.2;q24). Mental retardation, autosomal dominant 4 (MRD4) [MIM:612581]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the immunoglobulin superfamily. Contains 5 Ig-like C2-type (immunoglobulin-like) domains.
Sequence caution	The sequence AAQ89120.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB47496.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Mental retardation
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB neuron migration Inferred from electronic annotation. Source: Compara principal sensory nucleus of trigeminal nerve development Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara dendritic shaft Inferred from electronic annotation. Source: Compara extracellular region Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IZU9-1)

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: Q8IZU9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     566-600: NLKGVVSAKNDIRVEIVHKEPASGREGEEHSTIKQ → STGGRSGISGRGTEKKARLRLPRRASKQECNEQGS
     601-778: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 778

757

Kin of IRRE-like protein 3

PRO_0000015098

Regions

Topological domain

22 – 535

514

Extracellular Potential

Transmembrane

536 – 556

21

Helical; Potential

Topological domain

557 – 778

222

Cytoplasmic Potential

Domain

48 – 142

95

Ig-like C2-type 1

Domain

147 – 243

97

Ig-like C2-type 2

Domain

249 – 330

82

Ig-like C2-type 3

Domain

335 – 415

81

Ig-like C2-type 4

Domain

419 – 515

97

Ig-like C2-type 5

Compositional bias

701 – 767

67

Ser-rich

Amino acid modifications

Glycosylation

167

1

N-linked (GlcNAc...) Potential

Glycosylation

253

1

N-linked (GlcNAc...) Potential

Glycosylation

324

1

N-linked (GlcNAc...) Potential

Glycosylation

498

1

N-linked (GlcNAc...) Potential

Disulfide bond

69 ↔ 127

By similarity

Disulfide bond

170 ↔ 227

By similarity

Disulfide bond

271 ↔ 314

By similarity

Disulfide bond

356 ↔ 398

By similarity

Disulfide bond

440 ↔ 499

By similarity

Natural variations

Alternative sequence

566 – 600

35

NLKGV…STIKQ → STGGRSGISGRGTEKKARLR LPRRASKQECNEQGS in isoform 2.

VSP_011799

Alternative sequence

601 – 778

178

Missing in isoform 2.

VSP_011800

Natural variant

40

1

R → W in MRD4. Ref.6

VAR_054828

Natural variant

336

1

R → Q in MRD4. Ref.6

VAR_054829

Natural variant

731

1

V → F in MRD4. Ref.6

VAR_054830

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

778

Helix Strand Turn

Details...

Beta strand

422 – 425

4

Beta strand

440 – 442

3

Beta strand

449 – 457

9

Beta strand

462 – 465

4

Beta strand

468 – 475

8

Beta strand

478 – 484

7

Helix

490 – 494

5

Beta strand

497 – 502

6

Beta strand

507 – 512

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 8AD1694D3B376B0A	FASTA	778	85,255
	10 20 30 40 50 60 MKPFQLDLLF VCFFLFSQEL GLQKRGCCLV LGYMAKDKFR RMNEGQVYSF SQQPQDQVVV 70 80 90 100 110 120 SGQPVTLLCA IPEYDGFVLW IKDGLALGVG RDLSSYPQYL VVGNHLSGEH HLKILRAELQ 130 140 150 160 170 180 DDAVYECQAI QAAIRSRPAR LTVLVPPDDP VILGGPVISL RAGDPLNLTC HADNAKPAAS 190 200 210 220 230 240 IIWLRKGEVI NGATYSKTLL RDGKRESIVS TLFISPGDVE NGQSIVCRAT NKAIPGGKET 250 260 270 280 290 300 SVTIDIQHPP LVNLSVEPQP VLEDNVVTFH CSAKANPAVT QYRWAKRGQI IKEASGEVYR 310 320 330 340 350 360 TTVDYTYFSE PVSCEVTNAL GSTNLSRTVD VYFGPRMTTE PQSLLVDLGS DAIFSCAWTG 370 380 390 400 410 420 NPSLTIVWMK RGSGVVLSNE KTLTLKSVRQ EDAGKYVCRA VVPRVGAGER EVTLTVNGPP 430 440 450 460 470 480 IISSTQTQHA LHGEKGQIKC FIRSTPPPDR IAWSWKENVL ESGTSGRYTV ETISTEEGVI 490 500 510 520 530 540 STLTISNIVR ADFQTIYNCT AWNSFGSDTE IIRLKEQGSE MKSGAGLEAE SVPMAVIIGV 550 560 570 580 590 600 AVGAGVAFLV LMATIVAFCC ARSQRNLKGV VSAKNDIRVE IVHKEPASGR EGEEHSTIKQ 610 620 630 640 650 660 LMMDRGEFQQ DSVLKQLEVL KEEEKEFQNL KDPTNGYYSV NTFKEHHSTP TISLSSCQPD 670 680 690 700 710 720 LRPAGKQRVP TGMSFTNIYS TLSGQGRLYD YGQRFVLGMG SSSIELCERE FQRGSLSDSS 730 740 750 760 770 SFLDTQCDSS VSSSGKQDGY VQFDKASKAS ASSSHHSQSS SQNSDPSRPL QRRMQTHV
	Isoform 2 [UniParc]. Checksum: 67D52A6373036380	FASTA	600	65,308
	10 20 30 40 50 60 MKPFQLDLLF VCFFLFSQEL GLQKRGCCLV LGYMAKDKFR RMNEGQVYSF SQQPQDQVVV 70 80 90 100 110 120 SGQPVTLLCA IPEYDGFVLW IKDGLALGVG RDLSSYPQYL VVGNHLSGEH HLKILRAELQ 130 140 150 160 170 180 DDAVYECQAI QAAIRSRPAR LTVLVPPDDP VILGGPVISL RAGDPLNLTC HADNAKPAAS 190 200 210 220 230 240 IIWLRKGEVI NGATYSKTLL RDGKRESIVS TLFISPGDVE NGQSIVCRAT NKAIPGGKET 250 260 270 280 290 300 SVTIDIQHPP LVNLSVEPQP VLEDNVVTFH CSAKANPAVT QYRWAKRGQI IKEASGEVYR 310 320 330 340 350 360 TTVDYTYFSE PVSCEVTNAL GSTNLSRTVD VYFGPRMTTE PQSLLVDLGS DAIFSCAWTG 370 380 390 400 410 420 NPSLTIVWMK RGSGVVLSNE KTLTLKSVRQ EDAGKYVCRA VVPRVGAGER EVTLTVNGPP 430 440 450 460 470 480 IISSTQTQHA LHGEKGQIKC FIRSTPPPDR IAWSWKENVL ESGTSGRYTV ETISTEEGVI 490 500 510 520 530 540 STLTISNIVR ADFQTIYNCT AWNSFGSDTE IIRLKEQGSE MKSGAGLEAE SVPMAVIIGV 550 560 570 580 590 600 AVGAGVAFLV LMATIVAFCC ARSQRSTGGR SGISGRGTEK KARLRLPRRA SKQECNEQGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NEPH1 defines a novel family of podocin interacting proteins." Sellin L., Huber T.B., Gerke P., Quack I., Pavenstaedt H., Walz G. FASEB J. 17:115-117(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH NPHS2. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O. DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 491-778 (ISOFORM 1).
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"Solution structure of the fifth Ig-like domain of human kin of IRRE-like 3." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 413-521.
[6]	"Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability." Bhalla K., Luo Y., Buchan T., Beachem M.A., Guzauskas G.F., Ladd S., Bratcher S.J., Schroer R.J., Balsamo J., DuPont B.R., Lilien J., Srivastava A.K. Am. J. Hum. Genet. 83:703-713(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MRD4 TRP-40; GLN-336 AND PHE-731, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH CASK, CHROMOSOMAL TRANSLOCATION WITH CDH15.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF480410 mRNA. Translation: AAN73042.1.
AB058770 mRNA. Translation: BAB47496.1. Different initiation.
AY358743 mRNA. Translation: AAQ89103.1.
AY358760 mRNA. Translation: AAQ89120.1. Different initiation.
BC101775 mRNA. Translation: AAI01776.1.
BC101801 mRNA. Translation: AAI01802.1.

IPI

IPI00218082.
IPI00432312.

RefSeq

NP_001155179.1. NM_001161707.1.
NP_115920.1. NM_032531.3.

UniGene

Hs.376015.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CRY	NMR	-	A	413-521	[»]

ProteinModelPortal

Q8IZU9.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000278934.

PTM databases

PhosphoSite

Q8IZU9.

Polymorphism databases

DMDM

55736065.

Proteomic databases

PaxDb

Q8IZU9.

PRIDE

Q8IZU9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000525144; ENSP00000435466; ENSG00000149571.
ENST00000525704; ENSP00000435094; ENSG00000149571.

GeneID

84623.

KEGG

hsa:84623.

UCSC

uc001qea.3. human.
uc001qec.1. human.

Organism-specific databases

CTD

84623.

GeneCards

GC11M126326.

HGNC

HGNC:23204. KIRREL3.

HPA

HPA053324.

MIM

607761. gene.
612581. phenotype.

neXtProt

NX_Q8IZU9.

Orphanet

178469. Autosomal dominant nonsyndromic intellectual deficit.

PharmGKB

PA134958283.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG295274.

HOGENOM

HOG000020211.

HOVERGEN

HBG052260.

InParanoid

Q8IZU9.

OMA

KFHCSAK.

OrthoDB

EOG4TTGH9.

Enzyme and pathway databases

Reactome

REACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpress

Q8IZU9.

Bgee

Q8IZU9.

CleanEx

HS_KIRREL3.

Genevestigator

Q8IZU9.

GermOnline

ENSG00000149571. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 5 hits.

InterPro

IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]

Pfam

PF08205. C2-set_2. 1 hit.
PF07679. I-set. 3 hits.
[Graphical view]

SMART

SM00409. IG. 3 hits.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 5 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8IZU9.

GenomeRNAi

84623.

NextBio

74516.

SOURCE

Search...

Entry information

Entry name

KIRR3_HUMAN

Accession

Primary (citable) accession number: Q8IZU9
Secondary accession number(s): Q3MIJ7 , Q6UWJ9, Q6UWL5, Q96JG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2004
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.